We have demonstrated that ilimaquinone, a marine natural product, vesiculates Golgi membrane and depolymerizes cytoplasmic microtubules [Cell, 73, 1079 (1993), and J. Cell. Biol., 122, 1197 (1993)]. We have synthesized various derivatives of ilimaquinone in order to gain insight into the mechanism by which ilimaquinone affects these cytoplasmic structures. We have also coupled ilimaquine (or its synthetic derivatives) to agarose supports. Preliminary findings indicate that, in vitro, ilimaquinone binds to its target protein covalently and cannot, therefore, be eluted from the column. We will use a radiolabelled derivative of ilimaquinone to identify the cognate binding polypeptide(s). The only ilimaquinone derivative active in vesiculating Golgi membranes is the hydrogenated-ilimaquinone. The tritiated-ilimaquinone will allow us to recognize the binding protein by electrophoretic analysis detergent solubilized Golgi membranes. The ilimaquinone binding protein will be sequenced and cloned for further analysis of its role in ilimaquinone mediated Golgi vesiculation.